Religiosity and Telomere Length: Moderating Effect of Religiosity on the Relationship Between High-Risk Polymorphisms of the Apolipoprotein E and TOMM40 Gene and Telomere Length

Abstract

Objective: The current study seeks to examine the relationship between religiosity and telomere length (TL) in an older Chinese Muslim sample and to explore the moderating effect of religiosity on the relationship between high-risk polymorphisms and TL. Methods: A cross-sectional study of 1,692 community-dwelling adults aged 55 or older was conducted. Apolipoprotein E and TOMM40 (rs2075650) gene polymorphisms and TL were determined using standard procedures. Ordinal logistic regression was used to examine the associations. Results: Religiosity was significantly and positively related to TL. A significant interaction emerged between religiosity and the rs2075650 G polymorphism in predicting TL. Stratified multivariate analyses demonstrated that the relationship between the rs2075650 G state and TL was particularly strong among those who were more religious, as hypothesized. Conclusion: The findings revealed that religiosity may influence cellular aging in part by modifying the effect that high-risk genes have on increasing vulnerability to dementia and cognitive impairment.

Keywords

religiosity telomere length interaction

Introduction

Telomeres are complexes of repeat nucleotide sequences and binding proteins located at the ends of chromosomes that contain TTAGGG tandem repeats and can protect chromosomes from fusion, recombination, and degradation (Ellehoj, Bendix, & Osler, 2016; Rizvi, Raza, & Mahdi, 2014). Telomere length (TL) is greatest at birth and decreases progressively with advancing age, and as a result is considered a biomarker of chronological aging (Rizvi et al., 2014; Zhu, Belcher, & van der Harst, 2011). The decrease in the mean TL is 20 to 50 bp/year (Harley, Futcher, & Greider, 1990; von Zglinicki et al., 2000). TL is determined by several factors, including telomerase activity, rate of cell division, and oxidative stress, which is determined by genetic and environmental factors. The association between TL, cellular aging, and overall longevity has been demonstrated (Maximov et al., 2017; Rizvi et al., 2014). TL can also be affected by health behaviors such as drinking sugar-sweetened beverages, excessive alcohol consumption (Pavanello et al., 2011), smoking (Valdes et al., 2005), mental health (Needham et al., 2015; Phillips et al., 2013; Simon et al., 2006), and a variety of life stressors (Savolainen et al., 2014; Verhoeven et al., 2015).

Genome-wide association studies have found that TL is influenced by genetic polymorphisms (Delgado et al., 2017; Mangino et al., 2015), and more than 150 genes may be involved in telomere regulation (Gatbonton et al.,2006). Apolipoprotein E (ApoE), a plasma protein involved in the metabolism of lipoproteins and cholesterol, is the most important carrier protein in the nervous system (Mahley, 1988). Three alleles (ε2, ε3, and ε4) and six different genotypes (ε2/2, ε3/3, ε4/4, ε2/3, ε2/4, ε3/4) exist for ApoE (Hanlon & Rubinsztein, 1995). Research has shown that Apo E-knockout mice exhibit many aging features, such as loss of hair follicles, fading of hair, degradation of spermatogenic cells and seminiferous tubules, and a shortened lifespan, suggesting that ApoE may play an important role in aging (Chen & Yang, 2010). The ε4 allele carrier is associated with higher oxidative stress and a pro-inflammatory state (Jofre-Monseny, Minihane & Rimbach, 2010), which leads to DNA damage and telomere shortening.

Translocase of the Outer Mitochondrial Membrane-40kD (TOMM40) is a key channel in the mitochondrial outer cell membrane for the passage of various enzymes into the mitochondria, which has a direct effect on mitochondrial function. The TOMM40 gene and ApoE gene are located at same chromosome of 19 in the 45,312,338 to 45,422,606 area (Roses et al., 2013). A G/A polymorphism (rs2075650) in the second intron locus 45,395,619 is associated with longevity (Deelen et al., 2011), and the rs2075650 (allele G) may increase the risk of developing later onset Alzheimer disease (Bagnoli et al., 2013; similar to the Apo ε4 allele).

Religious involvement has been shown to play an important role in public health and has been associated with greater longevity in several studies. Research also indicates that adults who attend religious services, pray regularly, and consider themselves religious tend to exhibit longer telomeres than those who are less religiously involved (Hill, Ellison, Burdette, Taylor, & Friedman, 2016). Koenig, Nelson, Shaw, Saxena, and Cohen (2016) reported a U-shaped relationship between religiosity and TL among female family caregivers, finding a positive relationship between religiosity and TL among those who were not at all religious (10% of the sample), but among those with any level of religiosity (90% of the sample) there was a positive relationship between increasing religiosity and TL. Different aspects of religiosity may help to explain the association with TL, including increased social support (Carroll, Diez Roux, Fitzpatrick, & Seeman, 2013), greater self-control (Desmond, Ulmer, & Bader, 2013), and lower psychological stress due to improved coping (Savolainen et al., 2014). Hill, Vaghela, Ellison, and Rote (2017) found that religious attendance may promote TL indirectly by reducing symptoms of depression and cigarette smoking among Americans aged 50 and older.

An increasing number of studies have focused on the interaction between environmental factors and genes in order to help explain the relationship between religion and health. Religious involvement has been hypothesized to counteract cellular aging by modifying the effect of genes that may promote disease. Research has shown that high religiosity may lower the risk of mild cognitive impairment in those without the protective Apo ε2 allele (Wang, Wang, Koenig, & Alshohaib, 2017). Another study has found that religion may buffer the effect of high-risk alcohol dehydrogenase enzyme polymorphisms on alcohol use disorders (Chartier et al., 2016).

The current study sought to examine the relationship among religiosity on TL and the moderating effect of religiosity on the relationship between high-risk genetic polymorphisms and TL via a gene × environment (G × E) paradigm in a sample of Chinese Muslims. We hypothesized that greater religiosity would be associated with longer TL and would buffer the negative effect of high-risk genetic polymorphisms on TL (see Figure 1).

Figure 1.

Theoretical model of the moderating effect of religiosity on the relationship between high-risk genetic polymorphisms and telomere length.

Method

Study Sample

Participants in this study were community residents who engaged in a community public heath examination from 2013 to 2016, one of the public health programs supported by the local Chinese government and carried out once a year. All residents aged 55 years or older are eligible for the program. A total of 2,340 participants completed a questionnaire, and 1,861 received a physical examination and provided blood samples for genetic analysis and TL testing. Of those, TL could not be determined for 126 blood samples, and 27 participants carrying the Apo ε2/4 genotype were excluded for technical reasons (Sun et al., 2011), resulting in 1,692 subjects who were included in the final analysis. Inclusion criteria were (a) having a physical address in the local area, (b) age 55 years or older, and (c) Muslim religious affiliation. Those who were unable to complete the survey due to vision or hearing disabilities or a history of serious physical illness were excluded.

TL Assay

All the participants underwent a physical examination at community health centers by physicians, and venous blood samples were obtained. A face-to-face interview was performed by trained medical students using a structured questionnaire to collect demographic information (age, gender, education level, living status, etc.). TL was measured by a quantitative polymerase chain reaction (qPCR)-based assay (O’Callaghan & Fenech, 2011). Genomic DNA was isolated from peripheral blood leukocytes that were stored at −80°C. The DNA concentration was quantified using a Nanodrop SD-1000 spectrophotometer, and the DNA was subsequently spun down and resuspended to ensure accurate and uniform concentrations. Agarose gel electrophoresis was used to detect the integrity and purity of the DNA. To produce high-purity DNA, the genomic DNA template was highly pure. The ratio of ultraviolet (UV) spectrophotometer readings at wavelengths of 260 and 280 nm were between 1.7 and 2.1.

Purified DNA samples were obtained by dilution of the concentrated DNA samples with PCR grade water (DNase/RNase Free) into 96-well plate with a fixed concentration of 5 ng/µL. This assay compared telomere repeat sequence copy number (T) with a reference single copy gene copy (36B4) number (S) in each sample. Standard curves were derived from serially diluted reference DNA. Ratios in the range specified indicate the presence of nucleic acid with low amounts of contaminating protein. Genomic DNA of this quality is suitable for the next qPCR test. TL was measured by a qPCR-based assay. The qPCR was performed under the following conditions: pre-denature at 95°C for 10 min, denature at 95°C for 15 s, anneal/extend at 60°C for 1 min, with fluorescence data collection for 40 cycles. The designs used the following primer sequences: 5′CGGTTTGTTTGGGTTTGGGTTTGGGTTTGG GTTTGGGTT3′ (forward), 5′GGCTTGCCTTACCCTTACCCTTACCCT TACCCTTACCCT3′ (reverse) for telomere sequence amplification and 5′CAGCAAGTGGGA AGGTGTAATCC3′ (forward), 5′CCCATTCTATCATCAACGGGTACAA 3′ (reverse) for 36B4 sequence amplification.

The assay compared telomere repeat sequence copy number (T) with a reference single copy gene copy number (S) in each sample. Standard curves were derived from serially diluted reference DNA. The T/S ratio was calculated from the average quantity of reference DNA found to match with each experimental sample for the copy number of the targeted template (for T: the number of telomere repeats and for S: the number of 36B4 gene copies; Delgado et al., 2017). All the tests were performed in a lab according to standard procedures.

ApoE and TOMM40 Gene Polymorphism Test

Single-nucleotide polymorphisms (SNPs) of the rs429358, rs7412, and rs2075650 genes were detected by a MassARRAY system (Sequenom, San Diego, CA, USA) using the chip-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry technology performed at a genetic testing company in China (BGI, Shenzhen). To control for accuracy, 460 DNA samples were retested using a high-resolution melting (HRM) curve method (Graham, Liew, Meadows, Lyon, & Wittwer, 2005) at the Biochip Ningxia Center following the manufacturer’s instructions. The results of the two different methods were identical, and the kappa value was equal to 1. The Hardy–Weinberg balance test was conducted by chi-square analysis (rs2075650, χ² = 0.44, p = .508; ApoE gene, χ² = 23.24, p = .250).

Religiosity

Religiosity was measured using the Chinese version of the five-item Duke University Religion Index (DUREL) scale, a brief measure of religious involvement widely used in the literature (Koenig & Büssing, 2010). The DUREL consists of five questions: (a) How often do you attend religious events or other religious meetings held in temple, mosque, or church? (b) How often do you spend time in private religious activities, such as meditation, prayer, or studying religious scriptures? (c) In my life, I experience the presence of the Divine; (d) My religious beliefs guide all my other dealings in life; and (e) I try hard to practice my religion in my relationships with people around me. Thus, this measure assesses participation in organized religious activity, personal religious activity, and intrinsic religiosity. The Chinese version has been shown to have solid reliability and validity in the Ningxia population, with Cronbach’s alphas in the range of .86 to .89 (Wang, Rong, & Koenig, 2014). The DUREL score in the current population ranged from 5 to 27, with a higher score indicating higher religiosity.

Statistical Analysis

Analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 24.0 (SPSS Inc., Chicago, IL, USA). Means and standard deviations were used to describe continuous variables; counts and proportions were used to describe categorical variables. Ordinal logistic regression modeling was used to evaluate the association of religiosity and TL and also to examine the interaction between religiosity and the high-risk genetic polymorphisms Apo ε4 allele and rs2075650 gene G carrier on TL. The ordinal dependent variable for the regression model was TL (1 = 0.04-, 2 = 0.79-, 3 = 1.09-, 4 = 1.53-5.04), given the non-normal distribution of TL scores. The independent variables were age group (1 = 55-59 years, 2 = 60-64 years, 3 = 65 years and above), gender (0 = male, 1 = female), education (1 = illiterate, 2 = primary, 3 = junior, 4 = senior and above), living status (0 = alone, 1 = non-alone), ε4 carrier (0 = yes, 1 = no), rs2075650 G carrier (0 = yes, 1 = no), and DUREL score. Statistical significance was set at p < .05 (two-sided test).

Results

Demographic Characteristics

The demographic characteristics of participants are displayed in Table 1. The average age of participants was 63.4 (SD = 4.6) years with a range of 55 to 74 years. Slightly more than half (53.0%) were female, 10.5% lived alone, and more than half (58.5%) were illiterate. The mean TL was 1.26 (SD = 0.73) and the mean DUREL score was 25.6 (SD = 2.4). Approximately one fifth of subjects were ε4 carriers or G carriers of rs2075650.

Table 1.

Demographic Characteristics of the Participants.

Variables	N = 1,692
Age, M (SD), years	63.4 (4.6)
Age group, n (%)
55-59	361 (21.3)
60-64	673 (39.8)
65 and older	658 (38.9)
Gender, female, n (%)	900 (53.2)
Education level, n (%)
Illiterate	989 (58.5)
Primary	425 (25.1)
Junior	191 (11.3)
Senior and above	87 (5.1)
Living alone, yes, n (%)	177 (10.5)
DUREL, M (SD)	25.6 (2.4)
TL, M (SD)	1.26 (0.73)
Apo ε4 carrier, yes	346 (20.4)
rs2075650G carrier, yes	336 (19.9)

Note. DUREL = Duke University Religious Index; TL = telomere length.

Bivariate Analyses of TL

As shown in Table 2, TL decreased with the increase in age (p<.05), as expected. Higher religiosity was associated with longer TL (β = 0.05, odds ratio [OR] = 1.05; 95% confidence interval [CI] = [1.01, 1.09], p = .005), again as hypothesized. Surprisingly, no association was found between either the Apo ε4 carrier state or the rs2075650 G allele carrier and TL.

Table 2.

Bivariate Analyses With Telomere Length as the Dependent Variable (N = 1,692).

Variables	B	SE	Wald χ²	p value	OR [95% CI]
Age group
65 and older (ref.)
60-64	0.25	0.01	6.47	.011	1.28 [1.06, 1.56]
55-59	0.31	0.12	6.98	.008	1.36 [1.08, 1.71]
Gender, male	−0.09	0.09	1.11	.293	0.91 [0.77, 1.08]
Education
Senior and above (ref.)
Junior	−0.30	0.23	1.75	.186	0.74 [0.47, 1.16]
Primary	−0.26	0.21	1.58	.209	0.77 [0.51, 1.16]
Illiterate	−0.29	0.20	2.14	.143	0.75 [0.50, 1.10]
Living alone, yes	−0.10	0.14	0.57	.452	0.90 [0.69, 1.18]
Apo ε4 carrier, yes	0.10	0.11	0.84	.359	1.10 [0.89, 1.36]
rs2075650G carrier, yes	0.16	0.12	2.04	.153	1.17 [0.94, 1.45]
DUREL	0.05	0.02	7.71	.005	1.05 [1.01, 1.09]

Note. OR = odds ratio; CI = confidence interval; DUREL = Duke University Religion Index.

Interaction With Religiosity in Multivariate Analyses

As shown in Table 3, a significant interaction was found between religiosity and the ε4 carrier state on TL (β = 0.13, OR = 1.13; 95% CI = [1.03, 1.26]; p = .015). There was also a significant interaction between religiosity and the rs2075650 genotype G carrier life on TL (OR = 1.11; 95% CI = [1.01, 1.22]; p = .044). As shown in Table 4, to interpret the meaning of these positive interactions, analyses were stratified by religiosity (DUREL = 27 vs. DUREL < 27). As hypothesized, religiosity moderated the relationship between the rs2075650 polymorphism at the TOMM40 gene and TL, such that the association between the rs2075650 polymorphism and TL was significantly positive among those with high religiosity (OR = 1.35, 95% CI = [1.01, 1.78], p = .040), but no association was found between the rs2075650 polymorphism and TL in those with low religiosity. With regard to the Apo ε4 polymorphism, no significant association was found with TL in either those with high or low religiosity.

Table 3.

Multivariate Analyses (Ordinal Logistic Regression) With Telomere Length as the Dependent Variable (N = 1,692).

Variables	B	SE	Wald χ²	p value	OR [95% CI]
Model 1
DUREL	0.03	0.02	2.20	.138	1.03 [0.99, 1.07]
Apo ε4 carrier	−3.14	1.34	5.52	.019	0.04 [0.01, 0.59]
ε4 carrier × DUREL	0.13	0.05	5.92	.015	1.13 [1.03, 1.26]
Model 2
DUREL	0.03	0.02	2.77	.096	1.04 [0.99, 1.08]
rs2075650G carrier	−2.44	1.29	3.56	.059	0.09 [0.01, 1.10]
rs2075650G carrier × DUREL	0.10	0.05	4.07	.044	1.11 [1.01, 1.22]

Note. All models were controlled for age, gender, education level, and living status. OR = odds ratio; CI = confidence interval; DUREL = Duke University Religion Index.

Table 4.

Ordinal Regression Analysis of the Relationship Between High-Risk Genetic Polymorphisms and Telomere Length Stratified by Religiosity.

Variable	High religiosity (n = 1,012)		Low religiosity (n = 680)
Variable	OR [95% CI]	p value	OR [95% CI]	p value
rs2075650	1.35 [1.01, 1.78]	.040	1.22 [0.70, 2.12]	.482
Apo ε4	1.25 [0.95, 1.65]	.113	0.92 [0.68, 1.22]	.612

Note. Both the regression models controlled for age, gender, education level, and living status. OR = odds ratio; CI = confidence interval; DUREL = Duke University Religion Index.

Discussion

To our knowledge, this is the first study from China to examine the relationship between religiosity and TL and to determine moderating effects of religiosity on the relationship between high-risk polymorphisms of the ApoE and TOMM40 genes and TL. A Chinese Muslim sample was examined in this study because of the high religiosity of this population group compared with Chinese elders with other religious affiliations, given that previous research had found that the positive association between religiosity and TL was particularly strong at higher levels of religiosity (Koenig et al., 2016).

Bivariate analysis in the present sample revealed a significant positive relationship between religiosity and TL, consistent with previous research in the United States (Hill et al., 2016; Koenig et al., 2016). As expected, age was significantly and inversely correlated with TL, as many previous studies have reported (Delgado et al., 2017; Muzumdar & Atzmon, 2012).

There was also a significant inverse association between ε4 allele carrier state and TL when controlling for demographics (Table 3), a finding consistent with previous research reporting that ε4 carriers are at increased risk of having shorter TL and at greater risk of cognitive decline and more rapid aging (Jacobs et al., 2013). However, the opposite result has also been reported, that is, that ε4 carriers have longer telomeres (Wikgren et al., 2012). Present study also found a trend toward a significant inverse relationship between rs2075650 genotype G and TL (p = .059), after controlling for demographics, which is consistent with prior research that found the G allele of rs2075650 (compared with the A allele) of the TOMM40 gene was associated with shorter longevity (Lu et al., 2014).

When analyses were stratified by high and low religiosity to further identify the nature of these interactions, religiosity was shown to buffer the relationship between the rs2075650 polymorphism of the TOMM40 gene and TL. This relationship was significant and positive only in those with high religiosity, whereas no relationship was found in those with low religiosity. Greater religiosity in Chinese Muslims, then, may be particularly protective in maintaining TL in high-risk polymorphisms of the TOMM40 gene. These findings are supported by a study of alcohol metabolism genes and religious involvement (Chartier et al., 2016), which found that a higher frequency of religious attendance was associated with a weaker relationship between alcohol dehydrogenase enzyme risk genes and alcohol consumption. Furthermore, a previous study also found a modifying effect for religiosity on the relationship between Apo ε4 carrier state and cognitive impairment (Wang et al., 2017).

As noted in the “Introduction” section, there were several aspects of religiosity that may have positive effects on TL (Koenig & Shohaib, 2014). First, the effects of religious belief on TL are likely due to improved coping in the face of increased life stress. Many people turn to religion for comfort when medically ill or stressed, so the effects of religiosity on TL, especially in persons with the high-risk polymorphisms, may be due to the presence of this coping resource, leading to less emotional distress and depression, thereby reducing oxidative stress and inflammation that leads to shorter telomeres.

For example, Yung-ChiehYen et al. (2007) reported that the high-risk polymorphisms may be correlated with severe depression in the elderly, and research has also shown that depressive and anxiety disorders are associated with shorter TL (Révész, Verhoeven, Milaneschi, & Penninx, 2016). Furthermore, religious activities increase social support and social interactions, as shown by Hopkins (2011). Finally, religious belief can limit unhealthy behaviors such as smoking, alcohol abuse, lack of exercise, and other health behaviors known to adversely affect TL (Alomari, Hamed, & Abu, 2014; Headey, Hoehne, & Wagner, 2014; Harley, Futcher & Greider, 1990; Valdes et al., 2005).

There is now a religious awakening occurring in China. The percentage of Chinese adults who indicate they practice religion has increased rapidly during the past several decades (from 7.0% in 2001 to 23.9% in 2007; Stark & Liu, 2011). Given the increasing rate of aging in the Chinese population, the present findings have relevance for understanding the psychosocial-spiritual influences on biological processes through gene–environment interactions involved in aging.

Limitations

The generalizability and interpretation of results from the present study are influenced by several limitations. First, this was a cross-sectional analysis that prevents making causal inferences from the relationships between religiosity and TL reported here. Second, participants in this study were from a region of China where more than 30% of the population is Muslim, and so caution should be exercised when extrapolating these results to Chinese adults living in different regions of the country and those with or without a religious affiliation. Third, the nonrandom nature of the sample may cause a selection bias, thus limiting the external validity of the findings. Finally, potential mediators of the relationship between religiosity and TL, such as social support, stress level, and depression, were not assessed; future studies, particularly those with longitudinal designs, should measure such mediators so that causal mechanisms can be assessed.

Conclusion

This study found a significant positive relationship between religiosity and TL in a large sample of older Chinese Muslims and a positive moderating effect for religiosity on the relationship between high-risk polymorphism of the TOMM40 genes and TL. These findings help explain the biological mechanisms (gene–environment interactions in particular) underlying the positive relationship between religious involvement and longevity now reported in many studies. Future prospective studies are needed to confirm these findings and identify psychosocial factors and indicators of inflammation and oxidative stress that may help to further explain the mechanisms underlying the relationship between religiosity and TL.

Footnotes

Acknowledgements

The authors sincerely thank the staffs at CDC for their assistant in the data collecting.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (81860599).

Institutional Review

This study was approved by the Institutional Review Board of the Ningxia Medical University (No. 2015151 and 2018115). All the participants provided written informed consent. Professor Zhizhong Wang from Ningxia Medical University is the principal investigator (PI).

ORCID iD

Zhizhong Wang

References

Alomari

Hamed

Abu

T. H.

(2015). The role of religion in the recovery from alcohol and substance abuse among Jordanian adults. Journal of Religion & Health, 54, 1268-1277. doi:10.1007/s10943-014-9868-5

Bagnoli

Piaceri

Tedde

Bessi

Sorbi

Nacmias

(2013). TOMM40 polymorphisms in Italian Alzheimer’s disease and frontotemporal dementia patients. Neurological Sciences, 34, 995-998. doi:10.1007/s10072-013-1425-6

Carroll

J. E.

Diez Roux

A. V.

Fitzpatrick

A. L.

Seeman

(2013). Low social support is associated with shorter leukocyte telomere length in late life. Psychosomatic Medicine, 75, 171-177. doi:10.1097/PSY.0b013e31828233bf

Chartier

K. G.

Dick

D. M.

Almasy

Chan

Aliev

Schuckit

M. A.

. . . Hesselbrock

V. M.

(2016). Interactions between alcohol metabolism genes and religious involvement in association with maximum drinks and alcohol dependence symptoms. Journal of Studies on Alcohol and Drugs, 77, 393-404. doi:10.15288/jsad.2016.77.393

Chen

Yang

D. C.

(2010). Relationship between ApoE gene and human senile diseases and application of ApoE knockout mice in human aging disease research. Chinese Journal of Gerontology, 30, 1151-1153.

Deelen

Beekman

H. W.

Helmer

Kuningas

Christiansen

. . . Slagboom

P. E.

(2011). Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell, 10, 686-698. doi:10.1111/j.1474-9726.2011.00705.x

Delgado

D. A.

Zhang

Chen

L. S.

Gao

Roy

Shinkle

. . . Pierce

B. L.

(2017). Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal. Journal of Medical Genetics, 55, 64-71. doi:10.1136/ jmedgenet-2017-104922

Desmond

S. A.

Ulmer

J. T.

Bader

C. D.

(2013). Religion, self-control, and substance use. Deviant Behavior, 34, 384-406. doi:10.1080/01639625.2012.726170

Ellehoj

Bendix

Osler

(2016). Leucocyte telomere length and risk of cardiovascular disease in a cohort of 1,397 Danish men and women. Cardiology, 133, 173-177. doi:10.1159/000441819

10.

Gatbonton

Imbesi

Nelson

Akey

J. M.

Ruderfer

D. M.

Kruglyak

. . . Bedalov

(2006). Telomere length as a quantitative trait: Genome-wide survey and genetic mapping of telomere length-control genes in yeast. PLoS Genet, 2, e35. doi:10.1371/journal.pgen.0020104

11.

Graham

Liew

Meadows

Lyon

Wittwer

C. T.

(2005). Distinguishing different DNA heterozygotes by high- resolution melting. Clinical Chemistry, 51, 1295-1298. doi:10.1373/clinchem.2005.051516

12.

Hanlon

C. S.

Rubinsztein

D. C.

(1995). Arginine residues at codons 112 and 158 in the apolipoprotein E gene correspond to the ancestral state in humans. Atherosclerosis, 112, 85-90. doi:10.1016/0021-9150(94)05402-5

13.

Harley

C. B.

Futcher

A. B.

Greider

C. W.

(1990). Telomeres shorten during ageing of human fibroblasts. Nature, 6274, 458-460. doi:10.1038/345458a0

14.

Headey

Hoehne

Wagner

G. G.

(2014). Does religion make you healthier and longer lived? Evidence for Germany. Social Indicators Research, 119, 1335-1361. doi:10.1007/s11205-013-0546-x

15.

Hill

T. D.

Ellison

C. G.

Burdette

A. M.

Taylor

Friedman

K. L.

(2016). Dimensions of religious involvement and leukocyte telomere length. Social Science & Medicine, 163, 168-175. doi:10.1016/j.socscimed.2016.04.032

16.

Hill

T. D.

Vaghela

Ellison

C. G.

Rote

(2017). Processes linking religious involvement and telomere length. Biodemography and Social Biology, 63, 167-188. doi:10.1080/19485565.2017.1311204

17.

Hopkins

(2011). Religion and social capital: Identity matters. Journal of Community & Applied Social Psychology, 21, 528-540. doi:10.1002/casp.1120

18.

Jacobs

E. G.

Kroenke

Lin

Epel

E. S.

Kenna

H. A.

Blackburn

E. H.

Rasgon

N. L.

(2013). Accelerated cell aging in female APOE-epsilon4 carriers: Implications for hormone therapy use. PLoS One, 8, e54713. doi:10.1371/journal.pone.0054713

19.

Jofre-Monseny

Minihane

A. M.

Rimbach

(2010). Impact of apoE genotype on oxidative stress, inflammation and disease risk. Molecular Nutrition & Food Research, 52, 131-145. doi:10.1002/mnfr.200700322

20.

Koenig

H. G

Büssing

(2010). The Duke University Religion Index (DUREL): A five-item measure for use in epidemiological studies. Religions, 1, 78-85. doi:10.3390/rel1010078

21.

Koenig

H. G.

Nelson

Shaw

S. F.

Saxena

Cohen

H. J.

(2016). Religious involvement and telomere length in women family caregivers. The Journal of Nervous and Mental Disease, 204, 36-42. doi:10.1097/NMD.0000000000000443

22.

Koenig

H. G.

Shohaib

S. A.

(2014). Health and well-being in Islamic societies. Switzerland: Springer. doi:10.1007/978-3-319-05873-3

23.

Guan

H. J.

Gong

Liu

X. Q.

Zhu

R. R.

Wang

Yang

Z. L.

(2014). Genetic variants in PVRL2-TOMM40-APOE region are associated with human longevity in a Han Chinese population. PLoS ONE, 9, e99580. doi:10.1371/journal.pone.0099580

24.

Mahley

R. W.

(1988). Apolipoprotein E. cholesterol transport protein with expanding role in cell biology. Science, 240, 622-630. doi:10.1126/science.3283935

25.

Mangino

Christiansen

Stone

Hunt

S. C.

Horvath

Eisenberg

D. T. A.

. . . Aviv

(2015). DCAF4, a novel gene associated with leucocyte telomere length. Journal of Medical Genetics, 52, 157-162. doi:10.1136/jmedgenet-2014-102681

26.

Maximov

V. N.

Malyutina

S. K.

Orlov

P. S.

Ivanoschuk

D. E.

Voropaeva

E. N.

Bobak

Voevoda

M. I.

(2017). Leukocyte telomere length as an aging marker and risk factor for human age-related diseases. Advances in Gerontology, 7, 101-106. doi:10.1134/s2079057017020102

27.

Muzumdar

Atzmon

(2012). Telomere length and aging. In Li

(Ed.), Reviews on selected topics of telomere biology (pp. 3-30). Rijeka, Croatia: InTech.

28.

Needham

B. L.

Mezuk

Bareis

Lin

Blackburn

E. H.

Epel

E. S.

(2015). Depression, anxiety and telomere length in young adults: Evidence from the national health and nutrition examination survey. Molecular Psychiatry, 20, 520-528. doi:10.1038/mp.2014.89

29.

O’Callaghan

N. J.

Fenech

(2011). A quantitative PCR method for measuring absolute telomere length. Biological Procedures Online, 13, 3. doi:10.1186/1480-9222-13-3

30.

Pavanello

Hoxha

Dioni

Bertazzi

P. A.

Snenghi

Nalesso

. . . Baccarelli

(2011). Shortened telomeres in individuals with abuse in alcohol consumption. International Journal of Cancer, 129, 983-992. doi:10.1002/ijc.25999

31.

Phillips

A. C.

Robertson

Carroll

Der

Shiels

P. G.

McGlynn

Benzeval

(2013). Do symptoms of depression predict telomere length? Evidence from the west of Scotland twenty-07 study. Psychosomatic Medicine, 75, 288-296. doi:10.1097/PSY.0b013e318289e6b5

32.

Révész

Verhoeven

J. E.

Milaneschi

Penninx

B. W.

(2016). Depressive and anxiety disorders and short leukocyte telomere length: Mediating effects of metabolic stress and lifestyle factors. Psychosomatic Medicine, 46, 2337-2349. doi:10.1017/S0033291716000891

33.

Rizvi

Raza

S. T.

Mahdi

(2014). Telomere length variations in aging and age-related diseases. Current Aging Science, 7, 161-167. doi:10.2174/1874609808666150122153151

34.

Roses

A. D.

Lutz

M. W.

Crenshaw

D. G.

Grossman

Saunders

A. M.

Gottschalk

W. K.

(2013). TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial. Alzheimer’s & Dementia, 9, 132-136. doi:10.1016/j.jalz.2012.10.009

35.

Savolainen

Eriksson

J. G.

Kananen

Kajantie

A. K.

Heinonen

Räikkönen

(2014). Associations between early life stress, self-reported traumatic experiences across the lifespan and leukocyte telomere length in elderly adults. Biological Psychology, 97, 35-42. doi:10.1016/j.biopsycho.2014.02.002

36.

Simon

N. M.

Smoller

J. W.

McNamara

K. L.

Maser

R. S.

Zalta

A. K.

Pollack

M. H.

. . . Wong

K. K.

(2006). Telomere shortening and mood disorders: Preliminary support for a chronic stress model of accelerated aging. Biological Psychology, 60, 432-435. doi:10.1016/j.biopsycho.2014.02.002

37.

Stark

Liu

E. Y.

(2011). The religious awakening in china. Review of Religious Research, 52, 282-289. doi:10.2307/23055552

38.

Sun

Lim

Liu

Snellingen

Wang

Liu

(2011). Apolipoprotein E gene and age-related macular degeneration in a Chinese population. Molecular Vision, 17, 997-1002. doi:10.1038/emboj.2011.88

39.

Valdes

A. M.

Andrew

Gardner

J. P.

Kimura

Oelsner

Cherkas

L. F.

. . . Spector

T. D.

(2005). Obesity, cigarette smoking, and telomere length in women. The Lancet, 366, 662-624. doi:10.1016/s0140-6736(05)66630-5

40.

Verhoeven

J.E.

Révész

van Oppen

Epel

E.S.

Wolkowitz

O.M.

Penninx

B.W.

(2015). Anxiety disorders and accelerated cellular ageing. Br J Psychiatry, 206, 371-378. doi:10.1192/bjp.bp.114.151027

41.

von Zglinicki

Serra

Lorenz

Saretzki

Lenzen-Grossimlighaus

Gessner

. . . Steinhagen

. (2000). Short telomeres in patients with vascular dementia: An indicator of low antioxidative capacity and a possible risk factor? Laboratory Investigation, 80, 1739-1747. doi:10.1038/labinvest.3780184

42.

Wang

L. Q.

Wang

Z. Z.

Koenig

H. G.

Alshohaib

(2017). Interactions between apolipoprotein E genes and religiosity in relation to mild cognitive impairment. Neuropsychiatry, 7, 659-666. doi:10.4172/Neuropsychiatry.1000262

43.

Wang

Z. Z.

Rong

Koenig

H. G.

(2014). Psychometric properties of a Chinese version of the duke University religion index in college students and community residents in China. Psychological Reports, 115, 427-443. doi:10.2466/08.17.PR0.115c19z8

44.

Wikgren

Karlsson

Nilbrink

Nordfjäll

Hultdin

Sleegers

. . . Norrback

K. F.

(2012). APOE ε4 is associated with longer telomeres, and longer telomeres among ε4 carriers predicts worse episodic memory. Neurobiology of Aging, 33, 335-344. doi:10.1016/j.neurobiolaging.2010.03.004

45.

Yen

Y. C.

Rebok

G. W.

Gallo

J. J.

Yang

M. J.

Lung

F. W.

Shih

C. H.

(2007). ApoE4 allele is associated with late-life depression: A population-based study. The American Journal of Geriatric Psychiatry, 15, 858-868. doi:10.1097/JGP.0b013e3180f63373

46.

Zhu

Belcher

van der Harst

(2011). Healthy aging and disease: Role for telomere biology? Clinical Science, 120, 427-440. doi:10.1042/CS20100385